Systemic rheumatic diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and scleroderma, all have increased prevalence and severity in Native American communities. The serious burden of these chronically multisystem and incredibly morbid diseases on the welfare of tribal members in Oklahoma and elsewhere is compounded by limitations to care influenced by stretched health care systems, workforce issues and unique difficulties with clinical diagnosis and management. Bill Anoatubby, governor of the Chickasaw Nation, in an address to the U.S. Senate Committee on Indian Affairs, outlined the serious problems raised by the inability of tribal nations to obtain adequate and timely access to rheumatic disease care or to total joint replacements for patients with end-stage arthritis (or the prevention thereof). In addition, work by our group and others has shown that people with Native American heritage have clinical presentations which overlap established diseases which can delay their care and/or impair their response to standard therapy. Better understanding of the serologic markers which could help identify the primary disease process in these individuals would improve diagnosis and treatment selection for tribal members. Our rheumatology section has over three decades experience in the identification and management of systemic rheumatic diseases in Native American communities and in understanding (and even identifying new) serologic markers in these disorders. To support clinical research, we bring this experience, technology, xpertise and training skills to the Chickasaw and Cherokee nations by providing access to care and recruiting appropriate patients to provide serum samples to identify serologic markers which correlate with clinical presentations and disease outcome. This project seeks to establish a rheumatology clinic for citizens of each tribal nation to provide access to care, improve diagnosis/early treatment, and enroll individuals for serologic testing, to establish the prevalence and overlap of systemic rheumatic disease within these tribal communities, to define the serologic and clinical features which differentiate the rheumatic disease of tribal members with European-American and African-American counterparts to aid in refinement/improvement of diagnosis and clinical care, and most importantly to understand the pathogenesis of unique fine specificity autoimmune responses in Native American patient disease processes. This unique research opportunity will also serve as an ideal vehicle for training Native American students interested in biomedical research. A bright Chickasaw tribal member who plans to pursue a combined MD-PhD degree is already involved.